2aq0

From Proteopedia

(Difference between revisions)

Revision as of 00:30, 30 September 2014

Solution structure of the human homodimeric dna repair protein XPF

Structural highlights

2aq0 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ERCC4, ERCC11, XPF (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[ERCC4_HUMAN] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:278760]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.^[1] ^[2] ^[3] Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.^[4]

Function

[ERCC4_HUMAN] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The human XPF-ERCC1 protein complex plays an essential role in nucleotide excision repair by catalysing positioned nicking of a DNA strand at the 5' side of the damage. We have recently solved the structure of the heterodimeric complex of the C-terminal domains of XPF and ERCC1 (Tripsianes et al., Structure 2005;13:1849-1858). We found that this complex comprises a pseudo twofold symmetry axis and that the helix-hairpin-helix motif of ERCC1 is required for DNA binding, whereas the corresponding domain of XPF is functioning as a scaffold for complex formation with ERCC1. Despite the functional importance of heterodimerization, the C-terminal domain of XPF can also form homodimers in vitro. We here compare the stabilities of homodimeric and heterodimeric complexes of the C-terminal domains of XPF and ERCC1. The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the HhH domains of the two complexes. The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability.

The HhH domain of the human DNA repair protein XPF forms stable homodimers.,Das D, Tripsianes K, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R, Folkers GE Proteins. 2008 Mar;70(4):1551-63. PMID:17912758^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell. 1996 Sep 6;86(5):811-22. PMID:8797827
↑ Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet. 1998 Jun;7(6):969-74. PMID:9580660
↑ Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ. Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease. J Invest Dermatol. 1998 May;110(5):832-6. PMID:9579555 doi:10.1046/j.1523-1747.1998.00171.x
↑ Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006 Dec 21;444(7122):1038-43. PMID:17183314 doi:nature05456
↑ Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW. Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell. 2009 Jul 10;138(1):63-77. PMID:19596235 doi:S0092-8674(09)00777-6
↑ Das D, Tripsianes K, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R, Folkers GE. The HhH domain of the human DNA repair protein XPF forms stable homodimers. Proteins. 2008 Mar;70(4):1551-63. PMID:17912758 doi:http://dx.doi.org/10.1002/prot.21635

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2aq0"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_2aq0|  PDB=2aq0  |  SCENE=  }}
+==Solution structure of the human homodimeric dna repair protein XPF==
-===Solution structure of the human homodimeric dna repair protein XPF===
+<StructureSection load='2aq0' size='340' side='right' caption='[[2aq0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
-{{ABSTRACT_PUBMED_17912758}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2aq0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AQ0 FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERCC4, ERCC11, XPF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aq0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aq0 RCSB], [http://www.ebi.ac.uk/pdbsum/2aq0 PDBsum]</span></td></tr>
+<table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/ERCC4_HUMAN ERCC4_HUMAN]] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:[http://omim.org/entry/278760 278760]]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.<ref>PMID:8797827</ref> <ref>PMID:9580660</ref> <ref>PMID:9579555</ref>   Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:[http://omim.org/entry/610965 610965]]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.<ref>PMID:17183314</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/ERCC4_HUMAN ERCC4_HUMAN]] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.<ref>PMID:19596235</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aq/2aq0_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The human XPF-ERCC1 protein complex plays an essential role in nucleotide excision repair by catalysing positioned nicking of a DNA strand at the 5' side of the damage. We have recently solved the structure of the heterodimeric complex of the C-terminal domains of XPF and ERCC1 (Tripsianes et al., Structure 2005;13:1849-1858). We found that this complex comprises a pseudo twofold symmetry axis and that the helix-hairpin-helix motif of ERCC1 is required for DNA binding, whereas the corresponding domain of XPF is functioning as a scaffold for complex formation with ERCC1. Despite the functional importance of heterodimerization, the C-terminal domain of XPF can also form homodimers in vitro. We here compare the stabilities of homodimeric and heterodimeric complexes of the C-terminal domains of XPF and ERCC1. The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the HhH domains of the two complexes. The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability.
-==Disease==
+The HhH domain of the human DNA repair protein XPF forms stable homodimers.,Das D, Tripsianes K, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R, Folkers GE Proteins. 2008 Mar;70(4):1551-63. PMID:17912758<ref>PMID:17912758</ref>
-[[http://www.uniprot.org/uniprot/ERCC4_HUMAN ERCC4_HUMAN]] Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:[http://omim.org/entry/278760 278760]]; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.<ref>PMID:8797827</ref><ref>PMID:9580660</ref><ref>PMID:9579555</ref>  Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:[http://omim.org/entry/610965 610965]]. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.<ref>PMID:17183314</ref>
-==Function==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[http://www.uniprot.org/uniprot/ERCC4_HUMAN ERCC4_HUMAN]] Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.<ref>PMID:19596235</ref>
+</div>
+== References ==
-==About this Structure==
+<references/>
-[[2aq0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQ0 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:017912758</ref><references group="xtra"/><references/>
 [[Category: Homo sapiens]]
 [[Category: Boelens, R.]]

2aq0

From Proteopedia

Revision as of 00:30, 30 September 2014

Solution structure of the human homodimeric dna repair protein XPF

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox